Microsphere-Based Osteochondral Scaffolds Carrying Opposing Gradients Of Decellularized Cartilage And Demineralized Bone Matrix

Abstract

Extracellular matrix (ECM) “raw materials” such as demineralized bone matrix (DBM) and cartilage matrix have emerged as leading scaffolding materials for osteochondral regeneration owing to their capacity to facilitate progenitor/resident cell recruitment, infiltration, and differentiation without adding growth factors. Scaffolds comprising synthetic polymers are sturdy yet generally lack cues for guiding cell differentiation. We hypothesized that opposing gradients of decellularized cartilage (DCC) and DBM in polymeric microsphere-based scaffolds would provide superior regeneration compared to polymer-only scaffolds in vivo. Poly(D,L-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds were fabricated, either with opposing gradients of DCC and DBM encapsulated (GRADIENT) or without DCC and DBM (BLANK control), and implanted into rabbit osteochondral defects in medial femoral condyles. After 12 weeks, gross morphological evaluation showed that the repair tissue in about 30% of the implants was either slightly or significantly depressed, hinting toward rapid polymer degradation in scaffolds from both of the groups. Additionally, no differences were observed in gross morphology of the repair tissue between the BLANK and GRADIENT groups. Mechanical testing revealed no significant differences in model parameter values between the two groups. Histological observations demonstrated that the repair tissue in both of the groups was fibrous in nature with the cells demonstrating notable proliferation and matrix deposition activity. No adverse inflammatory response was observed in any of the implants from the two groups. Overall, the results emphasize the need to improve the technology in terms of altering the DBM and DCC concentrations, and tailoring the polymer degradation to these concentrations.